Search

Purpose: To analyze clinical outcome, local response, survival and toxicity in patients with primary cutaneous lymphoma (PCL) treated with radiotherapy. Methods: From 1995 to 2014, 112 patients were treated. B-cell lymphomas (CBCLs; n = 86) and T-cell lymphomas (CTCLs; n = 23) were analyzed separately. Clinical and therapeutic characteristics (age, sex, histology, primary treatment and radiotherapy modality) were related to response to treatment, survival and toxicity. Results: CBCLs were divided into 4 subgroups: marginal-zone lymphoma (n = 20), follicle center lymphoma (n = 32), diffuse large-cell lymphoma (DLBCL; n = 22) and DLBCL-leg type (n = 12). No significant correlation was found between doses and systemic treatments, extent of biopsy and number of lesions. DLBCL-leg type patients were older (p = 0.05), had disseminated disease (p = 0.034), and more frequently had local (p = 0.01) or systemic recurrence (p = 0.05). CTCLs were divided into 4 subgroups: α/β CTCL (n = 3), nasal type CTCL (n = 0), γ/δ CTCL (n = 10) and mycosis fungoides (n = 10). Longer disease-free survival was observed in patients obtaining complete remission (pConclusions: Radiotherapy is feasible, safe and effective for localized PCLs. The choice of dose is related to histological subgroups and the related prognoses. Survival results are very good also in relapsing disease. In advanced cutaneous lymphoma radiotherapy alone has mainly a role in symptom palliation.

Background Radiotherapy is one of the standard treatments for cutaneous lymphoma and Total Skin Electrons Beam Irradiation (TSEBI) is generally used to treat diffuse cutaneous lymphoma and some cases of localized disease. Helical IMRT (HI) allows to treat complex target with optimal dose distribution and organ at risk sparing, so helical tomotherapy has been proposed as alternative technique to TSEBI but only one preliminary report has been published. Methods Three patients treated (from May 2013 to December 2014) with Helical IMRT, with a total dose between 24 and 30 Gy, were retrospectively evaluated. Data about dosimetric features, response and acute toxicity were registered and analyzed. Planned target coverage was compared with daily in vivo measures and dose calculation based on volumetric images used for set up evaluation as well. Results The patients had a mean measured surface fraction dose ranging from 1.54 Gy up to 2.0 Gy. A planned target dose ranging from 85 to 120% of prescription doses was obtained. All doses to Organs At Risk were within the required constraints. Particular attention was posed on “whole bone marrow” planned V10Gy, V12Gy and V20Gy values, ranging respectively between 23 and 43%, 20.1 and 38% and 9.8 and 24%. A comparison with the theoretical homologous values obtained with TSEBI has shown much lower values with TSEBI. Even if treatment was given in sequence to the skin of the upper and lower hemi-body, all the patients had anaemia, requiring blood transfusions, leukopenia and thrombocytopenia. Conclusion Based on our limited results TSEBI should still be considered the standard method to treat total skin because of its pattern of acute and late toxicities and the dose distribution. In this particular case the better target coverage obtained with HI can be paid in terms of worse toxicity. Helical IMRT can instead be considered optimal in treating large, convex, cutaneous areas where it is difficult to use multiple electrons fields in relation with the clinical results and the limited and reversible toxicities.

New chemotherapeutic drugs and radiation therapy have significantly improved cancer patient’s survival, although the cardiovascular (CV) side effects of cancer treatment are increasingly important. In previous studies, an increased risk of cerebrovascular complications such as stroke and transient ischemic attack was described in patients undergoing neck radiotherapy. Aim: To evaluate vascular carotid structural (IMT, plaque) and functional (carotid stiffness) damage, and changes in arterial stiffness (Carotido-femoral pulse wave velocity; cf- PWV) in Hodgkin Lymphoma survivors previously treated with radiotherapy. Patients and methods: We enrolled206 Hodgkin lymphoma survivors (mean age 54±14years, 51%males, mean follow-up of9±6years).CV risk factors were investigated and atherosclerotic carotid damage was assessed by standard carotid ultrasound evaluation for intima-media thickness (IMT) measurement (MeanMax- IMT, CBMax, Tmax; n = 167); in 141 patients radiofrequency-based carotid stiffness analysis (distensibility; distensibility coefficient, DC; compliance coefficient; CC) was also performed.Cf-PWV measurement were obtained in 154 patients. Results: A significant correlation between radiotherapy dose and: MeanMax-IMT (r = 0.20; p < 0.05), Tmax (r = 0.20; p < 0.05), distensibility (r = 0.24; p < 0.05), DC(r = 0.24; p < 0.05), CC(r = 0.24; p < 0.05) was observed. Patients were divided into 4 groups according to radiotherapy dose (Dose: 20–30; 31–36; 37–42;>42Gy). An increase in Tmax (1.27±0.61, 1.35±0.59, 1.46±0.69, 1.76±1.12 mm, p for trend 42Gy), as compared to all the other dose groups (9.7±2.3 vs 8.3±2.2,8.0±1.5 and 8.3±1.4, p < 0.05). Conclusions: In this large number ofHL survivors, carotid IMT, plaque prevalence and aortic and carotid stiffness were significantly related with radiotherapy doses. Carotid IMT, carotid and aortic stiffness were significantly higher in the irradiated carotid arteries, but only at doses >42Gy, suggesting that there may be a dose threshold for radiotherapy-induced carotid wall damage.

To evaluate health-related quality of life (HRQL), social competence, and behavioral problems in children with perinatal HIV infection receiving highly active antiretroviral therapy (HAART), a cross-sectional study was performed at the Department of Pediatrics, University of Brescia. We evaluated HRQL, social competence, and behavioral problems in 27 HIV-infected children compared with age and sex-matched control subjects using the Pediatric Quality of Life Inventory (PedsQL) and the Child Behavior Checklist (CBCL), respectively. On the PedsQL 4.0 Generic Core Scale, HIV-infected subjects displayed significantly reduced physical (p=0.043) and psychosocial health (p=0.021) functioning, particularly at school (p=0.000), compared with healthy subjects, resulting in a significantly reduced total score (p=0.013). Assessment of social competence and the behavioral features of HIV-infected children by means of the CBCL revealed severe limitations of functioning in HIV-infected children who had impaired social ability. Children with HIV-RNA above the threshold level of 50 had higher scores on the CBCL delinquent behavior (p=0.021) and school competence (p=0.025) subsets. Although the introduction of HAART regimens has prolonged the survival of HIV-infected children, other factors, including disease morbidity and familial and environmental conditions, negatively affect their quality of life, thereby contributing to increased risk for behavioral problems. © 2010 Taylor & Francis.

Abstract 2773 Introduction. Infections during chemotherapy-induced aplasia are still a problem in the management of acute leukemia (AL) patients (pts), causing potentially life-threatening consequences and treatment delays. Adequate empiric antibiotic therapy is crucial for a favourable clinical evolution. In order to better define the best antimicrobial management for AL pts during different phases of treatment, we analyzed all infectious events occurring to consecutively treated AL pts at our Institute during a period of six years. Patients and Methods. Since June 2004 a program of active epidemiological surveillance is ongoing at our Institute. Data concerning infections occurring during chemotherapy-induced cytopenia in AL pts were analysed. All pts showing fever or signs/symptoms of infection underwent thorax X-ray and culture of any other fluid/drainage obtained from a suspected infection site. CT scan of thorax was performed when fever persisted >48h. An infection was considered clinically documented (CDI) when pertinent symptoms, objective signs, or diagnostic radiological findings were present and microbiologically documented (MDI) when microorganisms were isolated. Results. From June 2004 to May 2010, 210 cases of AL (154 acute myeloid leukemia [AML], 53 acute lymphoblastic leukemia [ALL], and 3 blastic plasmacytoid dendritic cell leukemia), were diagnosed and treated with at least one induction cycle followed by consolidation and with reinduction cycles in relapsing/refractory pts. Overall, 1014 chemotherapy cycles were delivered, subdivided as induction (I) (210), consolidation (C) (708) and salvage (S) (96) treatment. Overall 309 clinically documented infections (CDI) were observed (30.5%). Incidence of CDI was higher during S therapy in comparison with I or C (77.1% vs 41.9% and 20.7%, p Conclusions. The S phase has the highest infectious risk, particularly for BSI. Both prophylactic and empiric antibiotic therapy guided by epidemiological data seem warranted. In the I phase pneumonia, particularly of mycotic origin, is relatively more frequent, confirming the appropriateness of an effective antifungal prophylaxis. The C phase carries a very limited risk of life-threatening infections and a relatively high incidence of E. coli. Therefore, the need for antimicrobial and antifungal prophylaxis during C may be reconsidered. Overall the frequency of bacterial infections largely outweighs that of fungal infections and is responsible for 84% of infectious deaths. Among bacteria, P. aeruginosa ranks as the second more frequent microorganism after E. coli and carries the highest risk of death. Given its intrinsic ability of developing antibiotic resistance, it should be presently considered as the most threatening infectious agent in AL against which empiric antibiotic therapy should be tailored. Disclosures: No relevant conflicts of interest to declare.

Abstract 2149 Poster Board II-126 Background Autologous stem cell transplantation (ASCT) is a potentially curative treatment for lymphoma. Adequate stem cell (SC) collection is possible in the majority of cases but poor mobilization remains a major issue in some patients (pts). New agents were recently developed which may improve the rate of SC mobilization. Aims A retrospective analysis was conducted on a large series of lymphoma pts candidates to ASCT in order to identify factors influencing SC mobilization outcome. Potential early markers of poor mobilization were also evaluated. Patients and methods A total of 415 attempts of PBSC collection consecutively performed at 7 Italian centres in 388 pts affected by lymphoma were analyzed. Their median age was 52. A collection of less than 2×106 CD34+ cells/kg was defined as “mobilization failure” and of more than 5×106 CD34+ cells/kg as “good mobilization”. The following parameters were analysed for correlation with mobilization outcome: lymphoma diagnosis, disease status at mobilization, type of mobilizing chemotherapy, bone marrow infiltration at collection, n° of previous lines of therapy, prior use of fludarabine, alkylating agents or radiotherapy. The ratio between circulating CD34+cells/nL and total WBC/μL on the first day of CD34+ count (SCratio) was also analysed, trying to predict mobilization failure. Both univariate and multivariate statistical analyses were performed with SPSS package 13.0. Results Lymphoma diagnosis was diffuse large B cell/Burkitt in 38%, follicular in 10%, mantle in 13%, Hodgkin in 26%, T or NK/T in 6%, and other in 7% of cases. Disease status at apheresis was CR in 25%, chemosensitive in 49% and refractory in 26%. Mobilization was attempted during first-line therapy in 14%, in 37% during second-line and in 26% at third- or subsequent lines of therapy. Fludarabine, alkylating agents and extended-fields radiotherapy had been used prior to mobilization in 5%, 73% and 13% of cases respectively. Marrow infiltration by lymphoma was present in 17,7% and 7,7% of patients had failed a prior mobilization attempt. In 99% of cases (411/415) mobilizing therapy included chemotherapy and G-CSF. Two pts received AMD3100 and 2 G-CSF. Several chemotherapy programs were used for mobilization. For analysis purposes they were grouped as follows: single-agent cyclophosphamide (CTX) in 62 (15,1%); high-dose cytarabine, either single agent or in combination (HD-ARAC) in 143 (34,8%), etoposide-containing regimens in 119 (30,0%), and platinum containing regimens in 108 cases (26,3%). Mobilization failure occurred in 14% (59/415) whereas a good mobilization was obtained in 72% of cases. At univariate analysis mobilization failure was significantly associated with the use of single-agent CTX as mobilizer (p=0.000), with the n° of prior lines of treatment (p=0.006) and with failure of a previous mobilization attempt (p=0.000) whereas a diagnosis of follicular lymphoma (FL) was associated with a reduced risk of mobilization failure (p=0.007). Multivariate analysis confirmed FL as protective factor for mobilization failure (p=0.008) and single agent CTX and a higher n° of prior treatment lines as negative predictive factors (p=0.000 and 0.033 respectively). A “good mobilization” was significantly predicted at univariate analysis by HD-ARAC use as mobilizer (p=0,004) whereas single-agent CTX (p=0.000), n° of prior lines of therapy (p=0.005), prior fludarabine (p=0.035) or alkylating agents (p=0.003) were adverse predictors. Multivariate analysis confirmed HD-ARAC as independent predictive factor for good mobilization (p=0.031) and single-agent CTX and n° of prior lines of therapy as independent negative predictive factors (p=0.000 and 0.003 respectively). A SCratio of less than 10 on the first day of CD34+ count was associated with an increased risk of poor mobilization (p=0.000 risk estimate 0.638). Conclusions In this large series of pts with lymphoma the standard policy of SC mobilization was the use of chemotherapy + G-CSF. Nevertheless collection failed in a significant proportion of cases (14 %) and only 72% of cases reached an optimal SC collection. Predictive factors for mobilization outcome included disease and treatment history, type of lymphoma and type of mobilizing chemotherapy. These data provide the framework to rationally explore the use of new mobilizing agents in patients with lymphoma undergoing SC mobilization with chemotherapy and G-CSF. Disclosures: No relevant conflicts of interest to declare.

Abstract 4101 Background and aim The only curative option for adult patients with refractory or relapsed ALL is allogeneic haematopoietic stem cell transplant (allo-HSCT), which can offer a 28-34% long term survival in transplanted patients. However the actual feasibility of allo-HSCT is only 20-30% in unselected patients because of the low rate (30-50%) of complete remission (CR) achieved with salvage regimens (Tavernier, 2007- Thomas, 1999), the high rate of early relapse (Martino, 1999) and the difficulties in finding a suitable donor before progression (Davies, 1996). Hence, relapsed ALL can be actually cured in less than 10% of unselected adult patients. Using a second line treatment capable of obtaining a higher proportion of CR of longer duration may improve the dismal overall prognosis of patients. We report on the efficacy and toxicity profile of the combination of 6-metilprednisolone, mitoxantrone, etoposide and high-dose cytarabine (MECp), a salvage regimen containing cytostatic drugs to which patients had not been exposed during first line therapy, except for cytarabine at lower doses. Patients and Methods Between October 2000 and May 2009, 18 refractory/relapsed ALL patients were treated at our Institution with MECp regimen, consisting of a single course of etoposide 80mg/mq/die iv, cytarabine 1000mg/mq/die iv for 6 hours and mitoxantrone 6mg/mq/die iv 9 hours after cytarabine infusion for 6 days associated to metilprednisolone 50 mg/mq/die for 21 days, subsequently tapered to zero over one week. Three patients received an experimental sequential pulsed chemotherapy program in a multiinstitutional setting. At diagnosis, all patients had been treated according to the NILG-ALL 00/09 program (Bassan, Blood 2009). Four had been refractory to induction therapy and 14 had relapsed after a median of 12 months (range 3-43), 11 while on consolidation/maintenance, one after allo-HSCT, two after 3 and 12 months from the end of maintenance. There were 10 males and 8 females with a median age of 28 (range 17-64). ALL lineage was B in 9 cases (4 pro-B, 4 common, 1 pre B), T in 8 (5 pro-T, 3 cortical-TIII) and biphenotypic in 1. Molecular studies showed MLL/AF4 rearrangement in 3 and bcr/abl rearrangement in 3 cases, all before tyrosine-kinase inhibitors were available. Karyotypic abnormalities were present in 10 of 16 evaluable cases. Patients were treated in single/double bed rooms with reverse isolation. In 3 cases treatment duration was reduced to 4 days. Results CR was obtained in 13 of 18 patient (72,2%), independently of immunophenotype and time to relapse. CR rate was 100% in all ten patients with karyotypic abnormalities. Three patients (16%) died in aplasia during treatment, 2 of septic shock and 1 of unexplained shock. Two patients (T-ALL) were resistant. Recovery of neutrophils (>0,5×109/L) and platelets (>20×109/L) required a median of 22 days (range 17-37) and 28 days (range 21-45) from the start of therapy, respectively. Infections were documented in 9 of 18 (50%), being fatal in 2 (11%). Non-haematologic toxicity, mainly mucositis, was negligible. The median duration of CR was 5 months (range 2-5) which allowed 9 of 13 CR patients (69%) to undergo allo-HSCT (7 MUD, 1 HLA-identical sibling and 1 cord blood) after a median of 4 months (range 2-7) from CR. Reason for not being transplanted was failure of donor search in 4 patients who relapsed a median of 4 months. Causes of death included progressive disease in 7 patients, in 3 cases after HSCT, and transplant-related toxicity in 3 patients. The median survival of patients achieving CR was 13 months (range 7-33) and overall survival of the entire cohort was 8 months (range 1-33m). Conclusions With MECp, a combination of drugs not used during previous first-line therapy, a higher CR rate (72%) than commonly reported could be obtained, with acceptable toxicity. CR duration was long enough to allow 44,4% of patients to receive a non-family donor allo-HSCT, which is presently the best, yet still unsatisfactory, treatment option for adult patients with refractory/relapsed ALL. Disclosures: No relevant conflicts of interest to declare.